High density porous materials

ABSTRACT

Porous materials are disclosed having densities of at least about 6 pounds per cubic foot (96.1 kg/m 3 ). The materials comprise silica and/or alumina. 
     The porous materials are useful as supports for binding various chemical and biological molecules. The materials are useful as supports for analytical processes such as ELISA, blotting, and hybridization assays. The materials can be used as reinforcement agents for organic, inorganic, or metallic materials.

This application claims the benefit of Provisional App. No. 60/192,112,filed Mar. 24, 2000.

FIELD OF THE INVENTION

The invention relates to porous materials and, more specifically, toporous silica materials. The materials are useful for the binding ofchemical and biological molecules to be used in various analyticalmethods.

BACKGROUND OF THE INVENTION

Various plastic, glass, and membrane materials have historically beenused to bind chemical and biological molecules for use in variousanalytic methods such as ELISA, Western blotting, and hybridizations.

These materials are limited by their relatively low loading potential,and by their non-porous nature.

U.S. Pat. No. 5,951,295 (issued Sep. 14, 1999) describes ceramic fusedfiber enhanced dental materials, and methods for their preparation.Fused-fibrous material was taught comprising from about 1% to about 50%by weight alumina, from about 50% to about 98% silica, and from about 1%to about 5% by weight boron.

U.S. Pat. No. 5,964,745 (issued Oct. 12, 1999) describes an implantablesystem for bone or vascular tissue. The system comprises porous linkedfibrous biomaterial manufactured from nonwoven, randomly-oriented fiberslinked together using a fusion source at a plurality of cross-pointsinto a porous structure, said biomaterial having a plurality of voids ofa predetermined mean void size effective for stimulating angiogenesis insaid biomaterial from the tissue or bone.

U.S. Pat. No. 5,621,035 (issued Apr. 15, 1997) describes fillercompositions and ceramic enhanced dental materials. The preferredembodiment of the filler composition and the ceramic dental restorativematerial is comprised of about 22% by weight alumina, about 78% byweight silica, about 2% by weight silicon carbide, and about 2.85% byweight boron nitride with less than 1% cristobalite contamination.

Porous materials have been suggested by Yasukawa et al. (U.S. Pat. Nos.5,629,186 and 5,780,281). A composite was prepared from silica and/oralumina fibers with added boron nitride. The composites were suggestedas being useful for cell cultures, implants, and chromatographymatrices.

There exists a need for materials which bind chemical and biologicalmolecules while having improved surface properties.

SUMMARY OF THE INVENTION

Porous materials suitable for the binding of chemical and biologicalmolecules are disclosed. The three dimensional properties of thematerials results in improved loading properties. The materials can beused in a wide array of chemical and biological assays to improvesensitivities.

DETAILED DESCRIPTION OF THE INVENTION

Porous materials

A preferred embodiment of the invention is directed towards porousmaterials having densities of about 6 pounds per cubic foot (96.1 kg/m³)and higher, about 8 pounds per cubic foot (128 kg/m³) and higher, about12 pounds per cubic foot (192 kg/m³) and higher, about 24 pounds percubic foot (384 kg/m³) and higher, about 36 pounds per cubic foot (577kg/m³) and higher, about 48 pounds per cubic foot (769 kg/m³) andhigher, or about 64 pounds per cubic foot (1025 kg/m³) and higher. Thematerials can comprise up to about 100% silica, or up to about 60%alumina. The silica can be up to about 50% cristobalite, up to about 75%cristobalite, up to about 90% cristobalite, up to about 95%cristobalite, up to about 99% cristobalite, or can be about 100%cristobalite. The alumina can be aluminum borosilicate.

The exposed surface of the materials (“surface chemistry”) can be atleast about 50% silicon dioxide, at least about 75% silicon dioxide, atleast about 90% silicon dioxide, at least about 95% silicon dioxide, atleast about 99% silicon dioxide, or can be about 100% silicon dioxide.

The materials can comprise other metal oxides in addition to or in placeof the silica. For example, tantalum oxide or zirconium oxide can beincorporated into the materials.

The mean pore diameter of the materials can be less than 0.01 microns,about 0.1 micron to about 5 microns, up to about 10 microns, up to about20 microns, up to about 30 microns, up to about 40 microns, up to about50 microns, up to about 100 microns, up to about 200 microns, up toabout 300 microns, up to about 400 microns, up to about 500 microns, orup to about 600 microns. Ranges of pore diameter include about 0.1microns to about 1 micron, about 5 microns to about 10 microns, about 20microns to about 50 microns, about 100 to about 400 microns, or about200 microns to about 600 microns.

The surface properties of the materials can be modified by chemicalreactions. Examples include modifying the hydrophobicity orhydrophilicity of the porous materials, and hydroxylation withphosphoric acid.

The materials can be reinforced using an additional silica gel

The materials can further comprise carbon fiber, organic fiberscontaining carbon, or other polymer materials.

Preparation of Porous Materials

The preparation of porous materials is generally described in U.S. Pat.No. 5,951,295 (issued Sep. 14, 1999).

Porous materials can be prepared from: (1) from about 1% to about 50% byweight alumina; (2) from about 50% to about 98% by weight silica; and(3) from about 1% to about 5% by weight boron. In addition, thecomposition can further comprise silicon carbide up to about 3% byweight. The materials can comprise over 99% silica.

Generally, the process for preparing the porous materials can comprisethe following steps (as described in U.S. Pat. No. 5,951,295):

-   -   (1) preparation of a slurry mixture comprised of pre-measured        amounts of purified fibers/materials and deionized water;    -   (2) removal of shot from slurry mixture;    -   (3) removal of water after thorough mixing to form a soft        billet;    -   (4) addition of a ceramic binder after the formation of the        billet;    -   (5) placement of the billet in a drying microwave oven for        moisture removal; and    -   (6) sintering the dry billet in a large furnace at about        1600° F. or above.

The high purity silica fibers above are first washed and dispersed inhydrochloric acid and/or deionized water or other solvents. The ratio ofwashing solution to fiber is between 30 to 150 parts liquid (pH 3 to 4)to 1 part fiber. Washing for 2 to 4 hours generally removes the surfacechemical contamination and non-fibrous material (shot) which contributesto silica fiber devitrification. After washing, the fibers are rinsed 3times at approximately the same liquid to fiber ratio for 10 to 15minutes with deionized water. The pH is then about 6. Excess water isdrained off leaving a ratio of 5 to 10 parts water to 1 part fiber.During this wash and all following procedures, great care must be takento avoid contaminating the silica fibers. The use of polyethylene orstainless steel utensils and deionized water aids in avoiding suchcontamination. The washing procedure has little effect on the bulkchemical composition of the fiber. Its major function is theconditioning and dispersing of the silica fibers.

The alumina fibers are prepared by dispersing them in deionized water.They can be dispersed by mixing 10 to 40 parts water with 1 part fiberin a V-blender for 21/2 to 5 minutes. The time required is a function ofthe fiber length and diameter. In general, the larger the fiber, themore time required.

Generally, in order to manufacture low density porous materials, forexample, densities below 12 lb/ft³ ((192 kg/m³)), the process includesthe additional steps of:

-   -   (1) the addition of expendable carbon fibers in the casting        process and/or other temporary support material; and    -   (2) firing the billet at about 1300° F. to remove the carbon        fibers or other support material prior to the final firing at        approximately 1600° F. or above.

When the dispersed silica fibers and dispersed alumina fibers arecombined, the pH may be acidic, and if so, should be adjusted to neutralwith ammonium hydroxide. The slurry should contain about 12 to about 25parts water to about 1 part fiber. The slurry is mixed to a uniformconsistency in a V-blender in 5 to 20 minutes. The boron nitride can beadded at this point (2.85% by weight of the fibers) and mixed to auniform consistency in a V-blender for an additional 5 to 15 minutescreating a Master Slurry. The preferred mixing procedure uses 15 partswater to 1 part fiber and the slurry is produced in about 20 minutes ofmixing. At lower density formulations, expendable carbon fibers are usedto give “green” strength to the billet prior to the final sintering. Thepercent of carbon fiber used varies greatly depending on the diameter,length and source of the fiber and the ultimate density of the materialbeing produced. The percent of carbon fiber per dry weight of materialshould range between 1% and 10%. The source of the carbon fiber can takemany forms including nylon, cellulose, and purified graphite basedcarbon in fibrous form. Carbon fibers added in the casting process areeliminated by firing the billets at 1350° F. prior to the final firingat 2450° F.

The Master Slurry is poured into a mold for pressing into the desiredshape. The water is withdrawn rapidly and the resulting felt iscompressed at 10 to 20 psi. Rapid removal of the water is required toprevent the fibers from separating. If graded properties are desired inthe resultant material, the slurry can be allowed to settle and thefibers to partially separate before the removal of the water.

The final density of the finished restorative material is determined inpart by the amount of compression placed on the felt, varying the wetmolded dimension in relation to the fiber content. The formulation ofthe present invention has been prepared in densities ranging from about0.05 to 0.48 g/cc. It can, however, be prepared in lower and higherdensities.

After molding, the restorative material can be dried and fired by thefollowing procedure. The material is first dried in an oven for 18hours; the temperature, initially 38° C., is raised at a rate of 11° C.per hour to 104° C., held there for 4 hours, raised again at a rate of11° C. per hour to 150° C., and held there for 4 hours. The material istaken directly from the drying oven, placed in the firing furnace, andfired. A temperature rise rate of 220° C. per hour or less is requiredin order to avoid cracking and warping in the case of a 15 cm×15 cm×7.5cm block of material. For larger blocks, slower heating rates may berequired. The maximum firing temperature may vary from 1200° C. to 1600°C. depending upon the fiber ratio used, amount of boron nitride, and thefinal density of the material that is desired.

The temperature rise rate is chosen to permit relatively uniformtemperatures to be achieved throughout the material during the process.A faster temperature rise rate causes non-uniform temperatures to beachieved throughout the material during the process. A fastertemperature rise rate causes nonuniform strength and density and maycause cracking. Longer or higher temperature firing results in highershrinkage and related greater resistance to subsequent shrinkage, aswell as a shorter lifetime to devitrification under cyclic exposures tohigh temperatures. The maximum firing temperature is dependent upon thefiber ratio used and the density of the composite desired. The firingtime and maximum temperature are selected to allow sufficient shrinkageto achieve stabilization and fiber fusion while not allowing anydevitrification. After firing, the material may be machined to obtainany desired final dimensions.

The following method of preparing the porous material, and severalproposed uses, was described in U.S. Pat. No. 5,629,186.

Preparing the Matrix

In general, the method includes forming a fiber slurry having desiredviscosity and fiber dispersion characteristics, allowing the slurry tosettle under conditions that produce a selected fiber density andorientation, drying the resulting fiber block, and sintering the blockto form the desired fused-fiber matrix.

A. Fiber Treatment

The silica (SiO₂) and/or alumina (Al₂O₃) fibers used in preparing thematrix are available from a number of commercial sources, in selecteddiameters (fiber thicknesses) between about 0.5 μm–20 μm. A preferredsilica fiber is a high purity, amorphous silica fiber (99.7% pure), suchas fabricated by Manville Corporation (Denver, Colo.) and sold under thefiber designation of “Q-fiber”. High purity alumina fibers (average 3microns) may be procured, for example, from ICI Americas, Inc.(Wilmington, Del.).

In a preferred heat treatment, the silica fibers are compressed intopanels, e.g., using a Torit Exhaust System and compaction unit. Thecompressed panels are sent passed through a furnace, e.g., a HarperFuzzbelt furnace or equivalent at 2200° F. for 120 minutes,corresponding to a speed setting of about 2.7 inches/minute. The heattreatment is used to close up surface imperfections on the fibersurfaces, making the matrix more stable to thermal changes on sintering.The heat treatment also improves fiber chopping properties, reducingfabrication time.

In a preferred method, the heat-treated fibers are washed to removedebris and loose particles formed during fiber manufacturing.

B. Preparing a Fiber Slurry

Silica and/or alumina fibers from above are blended to form a fiberslurry that is used in forming a “green-state” block that can besintered to form the desired matrix.

The slurry is formed to contain, in an aqueous medium, silica, alumina,or silica and alumina fibers of the type described above, at afiber:liquid weight ratio of between about 1:25 to 1:70, where theliquid weight refers to the liquid weight of the final slurrypreparation.

The slurry preferably includes a thickening agent effective to give theslurry a viscosity between about 1,000 and 25,000 centipoise, asmeasured by standard methods. The viscosity agent may be any of a numberof well-known hydrophilic polymers, such as polyvinylalcohol,polyvinylacetate, polyvinylpyrrolidone, polyurethane, polyacrylamide,food thickeners, such as gum arabic, acacia, and guar gum, andmethacrylate type polymers. The polymers preferably have molecularweights greater than about 25–50 Kdaltons, and are effective to increasesolution viscosity significantly at concentrations typically betweenabout 0.5–10 weight percent solution.

Preferred thickening agents polymers that also have tacky or adhesiveproperties, such as methyl cellulose, terpolymers of maleic anhydride,alkyl vinyl ether, and an olefin (U.S. Pat. No. 5,034,486), copolymersof ethylene and olefins (U.S. Pat. No. 4,840,739), cellulose-containingpastes (U.S. Pat. No. 4,764,548), and soy polysaccharides. One preferredthickening agent is methylcellulose, e.g., the polymer sold under thetradename Methocel A4M and available from Dow Chemical Co. (Midland,Mich.).

Where the matrix is formed of high-purity silica fibers and/or alumina,the slurry is also formed to contain a source of boron that functions,during sintering, to form a boron/silica or boron/alumina surfaceeutectic that acts to lower the melting temperature of the fibers, attheir surfaces, to promote fiber/fiber fusion at the fiberintersections. In a preferred embodiment, the boron is supplied in theslurry as boron nitride particles 15 to 60 μm in size particles. Suchparticles can be obtained from Carborundum (Amherst, N.Y.). The amountof boron nitride is preferably present in the slurry in an amountconstituting between about 2–12 weight percent of the total fiberweight.

The adhesive property of the thickening agent described above is usefulin adhering particles of boron nitride and, if used, silicon carbide, tothe fibers in the slurry, to produce a relatively uniform of particlesin the slurry, and prevent the particles from settling out of slurryduring the molding process described below.

The slurry preferably also contains a dispersant which acts to coat thefibers and help disperse the fibers, both to increase slurry viscosity,and to prevent silica fibers from “bundling” and settling out of theslurry as fiber aggregates during the molding process described below.The dispersant is preferably one which imparts a significant chargeand/or hydrophilicity to the fibers, to keep the fibers separated duringslurry formation and settling during the molding process.

For use with silica fibers, ammonium salts are particularly useful asdispersants, because the ammonium cation is released from the matrix inthe form of ammonia during matrix drying and/or sintering. Preferredammonium salts are the salts of polyanionic polymers, such as ammoniumpolymethylmethacrylate, or the ammonium salt of other carboxylatedpolymers. One preferred dispersant agent is the ammoniumpolymethylmethacrylate polymer sold by R. T. Vanderbilt under thetradename Darvan 821A. The polymer dispersant is preferably added to theslurry to make up between about 0.2 to 5 percent of the total liquidvolume of the slurry.

The slurry may further contain between about 1–5 percent by weightsilicon carbide particles, such as obtainable from Washington MillsElectro Minerals Corp. (Niagara Fall, N.Y.).

A preferred method for preparing a slurry of the type just described isdetailed as follows. Briefly, heat-treated silica fibers are suspendedin water at a preferred fiber:water ratio of about 1:300 to 1:800. Thefiber slurry is pumped through a centrifugal cyclone to remove shotglass and other contaminants, such as high soda particles. The fibercake formed by centrifugation is cut into segments, dried at 550° F. forat least 8 hours, and then broken into smaller chunks for forming thematrix.

Fragments of the silica fiber cake are mixed in a desired weight ratiowith alumina fibers, and the fibers are dispersed in an aqueous solutioncontaining the dispersing agent. At this point, the fibers arepreferably chopped to a desired average fiber length in alow-shear/high-shear mixer. In general, the greater the degree ofchopping, the shorter the fibers, producing better packing and a lessopen matrix structure. Similarly, longer fibers lead to more open matrixstructure. The fiber mixing is preferably carried out under condition toproduce average fiber sizes of a selected size in the 1–10 mmfiber-length range.

After mixing, the fibers are allowed to settle, and the liquid/fiberratio is reduced by decanting off some of the dispersing liquid. To thisslurry is added an aqueous gel mixture formed of the viscosity agent,e.g., methyl cellulose, and the matrix particles, e.g., boron nitrideparticles, and the slurry components are mixed to form the desiredhigh-viscosity slurry. The slurry is now ready to be transferred to acasting mold, to prepare the green-state block, as described in the nextsection.

C. Forming a Dried Fiber Block

According to an important aspect of the method, the slurry is allowed tosettle and is dewatered in a fashion designed to achieve a relativelyuniform fiber density throughout the matrix, and relatively randomlyoriented fibers, i.e., with little a fiber orientation preference in thedirection of settling.

In the first step, a slurry is added to a mold equipped with a lowerscreen sized to retain slurry fibers. For fiber sizes in the range 1–10mm, the screen has a mesh size between about 8 to 20 squares/inch. Themold has a lower collection trough equipped with a drain and a vacuumport connected to a suitable vacuum source.

Initially, the slurry is added to the mold and, after stirring theslurry to release gas bubbles, is allowed to settled under gravity,until the level of water in the mold is about 1–2 inches above the levelof the desired final compaction height, i.e., the final height of thedewatered block. For a slurry of about 12 1 added to a 18 cm² squaremold, the initial settling takes about 3–10 minutes.

The partially drained slurry in the mold is now compacted with acompacting ram to force additional water from slurry. This is done byallowing the ram to act against the upper surface of the slurry underthe force of gravity, while draining the water forced through a screenfrom the mold. Water is squeezed from the slurry until the ram reachesthe desired compaction height. With the slurry volume and molddimensions just given, a ram having a weight of about 7 lbs is effectiveto compress the partially dewatered slurry in a period of about 0.2 to 2minutes.

In the final step of compacting and dewatering, the drain is closed andvacuum is applied to a port until the block is completely dewatered. Avacuum of between about 0.01 to 0.5 atm is effective to produce completedewatering of the mold in a period of about 0.2 to 5 minutes. The vacuumdewatering may result in the upper surface of the block pulling awayfrom the ram.

The dewatered block is now removed from the mold and dried in an oven,typically at a temperature between 250° F.–500° F. In the dried matrix,the viscosity agent, and to a lesser extent, the dispersant agent, actto bond the fibers at their intersections, forming a rigid, non-fusedblock. The target density of the matrix after drying is between about3.3 to 5.3 pounds/ft³.

The green-state matrix may be formed to include sacrificial fillerelement(s) that will be vaporized during sintering, leaving desiredvoids in the final fused matrix block. The filler elements arepreferably formed of polymer or graphite. An array of parallel rods maybe placed in the mold, at the time the slurry is added. Slurry settlingand dewatering are as described above, to form the desired green-stateblock with the included sacrificial element.

The first step is the slurry formation. The slurry may be a single fibersuspension containing a desired size range and fiber composition.Alternatively, for forming a discontinuous or step fiber matrix, two ormore slurries having different fiber thicknesses, densities, and/orfiber compositions may be formed.

After the slurry is introduced into the mold, the steps in settling anddewatering the slurry can be varied to produce either a continuousgradient of fiber density or a uniform fiber density. The steps informing a uniform gradient, including an initial settling step, followedby ram compaction and final dewatering by vacuum have been consideredabove.

To produce a continuous gradient of fiber densities, the slurry is firstsubjected by dewatering by vacuum, causing material closest to thescreen to be compacted preferentially. When a desired gradient isachieved, the slurry is gravity drained to dewater the slurry, thenram-compacted for further dewatering. The slurry may be subjected to afinal vacuum dewatering.

To produce a block having a series of discontinuous layers, each with auniform fiber density, each successive slurry is handled substantiallyas described above for the uniform-density block. The layers can beformed by successively casting layer upon layer in the mold, with eachsuccessive layer being compacted as described above. Alternatively, aseries of block layers, each with a distinctive fiber size/compositionand/or density is prepared. Before drying, the individual blocks areplaced together in layers, to form the desired discontinuous-layerblock. The layers may be “glued” together before drying by applying, forexample, a layer of boron nitride in the viscosity agent between thelayers.

D. Fused Fiber Matrix

In the final step of matrix formation, the green-state block from aboveis sintered under conditions effective to produce surface melting andfiber/fiber fusion at the fiber crossings. The sintering is carried outtypically by placing the green-state block on a prewarmed kiln car. Thematrix is then heated to progressively higher temperature, typicallyreaching at least 2,000° F., and preferably between about 2,200°F.–2,400° F., until a desired fusion and density are achieved, thetarget density being between 3.5 and 5.5 pounds/ft³. For a block formedsolely of alumina fibers, a maximum temperature of about 2,350° F. issuitable.

In a preferred method, discussed above, the matrix is formed withhigh-purity silica fibers that contain little or no contaminating boronand/or with alumina fibers that are also substantially free of boron. Inorder to achieve fiber softening and fusion above 2,000° F., typicallyin the temperature range 2,000° F.–2,200° F., it is necessary tointroduce boron into the matrix during the sintering process, to form asilica/boron or alumina/boron eutectic mixture at the fiber surface.Boron is preferably introduced, as detailed above, by including boronnitride particles in the green-state block, where the particles areevenly distributed through the block.

During sintering, the boron particles are converted to gaseous N₂ andboron, with the released boron diffusing into the surface of the heatedfibers to produce the desired surface eutectic, and fiber fusion. Thedistribution of boron particles within the heated block ensures arelatively uniform concentration of boron throughout the matrix, andthus uniform fusion properties throughout.

Also during fusion, the viscosity agent and dispersant agents used inpreparing the green-state block are combusted and driven from the block,leaving only the fiber components, and, if added, silicon carbideparticles.

Where the green-state block has been constructed to include asacrificial element, the sintering is also effective to vaporize thiselement, leaving desired voids in the matrix, such as a lattice ofchannels throughout the block.

After formation of the fused-fiber matrix, the matrix block may bemachined to produce the desired shape and configuration. For example,the matrix can be formed by drilling an array of channels in the block;or by cutting the block into thin plates.

Polymer Fiber Matrix

In another aspect, the invention includes a fibrous polymer matrix. Thematrix is composed of fused polymer fibers, and is characterized, in dryform, by: (a) a rigid, three-dimensionally continuous network of open,intercommunicating voids, and (b) a free volume of between about 90–98volume percent. The fibers may also include up to 80 percent by weightof either silica fibers, alumina fibers, or a combination of the twofibers types.

The matrix is designed for use particularly as a substrate for cellgrowth in vitro, and as such, contains an array of channels extendingthrough the matrix. In an alternative embodiment, the matrix has amulti-plate configuration.

The fused polymer matrix is formed substantially as described for thesilica, alumina, or silica/alumina fiber matrices described above, butwith the modifications now to be discussed.

The polymer fibers used in constructing the matrix may be anythermoplastic polymers that can be heat fused, typically when heated inthe range 400° F.–800° F. Exemplary polymer fibers include polyimide,polyurethane, polyethylene, polypropylene, polyether urethane,polyacrylate, polysulfone, polypropylene, polyetheretherketone,polyethyleneterphthalate, polystyrene, and polymer coated carbon fibers.Fibers formed of these polymers, and preferably having thickness in the0.5 to 20 μm range, can be obtained from commercial sources. The fibersmay be chopped, i.e., by shearing, to desired lengths, e.g., in the 0.1to 2 mm range, by subjecting a suspension of the fibers to shear in ahigh-shear blender, as described above.

The polymer fibers may be blended with up to 80 weight percent silicaand/or alumina fibers of the type described above. Preferably, thesilica fibers are heat treated to close up surface imperfections on thefiber surfaces, as described above. The alumina fibers may also be heattreated, e.g., under the sintering conditions described above, toproduce surface granulation on the fiber.

The aqueous fiber slurry used in preparing the matrix contains, inaddition to fibers, a viscosity agent effective to produce a finalslurry viscosity between about 1,000 and 25,000 centipoise. Viscosityagents of the type mentioned above are suitable. If the polymers fibersare relatively hydrophobic, or if the fibers include silica fibers, theslurry should contain a dispersant effective to prevent the fibers fromaggregating on settling. Such a dispersant may include surfactantsand/or charged polymers, and/or block copolymers, such aspolyethylene/polypropylene block copolymers known to enhance thehydrophilicity of polymer surfaces.

The slurry also contains an adhesive agent effect to retain thegreen-state fiber network in a rigid condition once it is formed. Eitherthe viscosity agent or dispersant may supply the necessary adhesiveproperties. Alternatively, a separate adhesive component may be added tothe slurry.

The above slurry is placed in a settling mold, as above, and the fibersare allowed to settle under dewatering conditions, substantially asdescribed above, to yield randomly oriented fibers having a desiredfiber density. The network is formed into a greenstate block by drying,e.g., at 100° F.–300° F.

In the final step, the greenstate block is heated under conditions,typically at a temperature between 400° F.–800° F., effective to producefiber fusion at the fiber points of intersection. The selectedtemperature is near the softening point of the thermoplastic polymer. Atthis temperature, the polymer fibers fuse with one another and withsilica and/or alumina fibers in the block to produce the desired rigid,fused fiber matrix.

Utility: Cell-Growth Substrate

The low-density matrix described above in the above sections is designedparticularly for use as a substrate for cell growth in vitro, or in vivoas an implantable substrate.

The architecture of the matrix, and particularly the characteristics ofa rigid, three-dimensionally continuous network of open,intercommunicating voids, and a free volume of between about 90–98volume percent, permit rapid cell growth in three dimensions.

In a preferred embodiment, the matrix is formed of silica fibers,typically in an amount between about 50–100 weight percent of the totalfiber weight. In another preferred embodiment, the matrix is formed toinclude alumina fibers, preferably heated to produce surfacegranulation, in an amount of fiber preferably between about 20–80 weightpercent fiber.

The silica and/or alumina fibers may enhance cell adhesion, and/oradhesion of growth factors, such as fibrofectin, vibronectin, orfibrinogen. Representative cell culture and cell implantationapplications are discussed below.

A. Cell Culture

In one general embodiment, the matrix of the invention is used tosupport cell growth in a cell culture system in vitro. A firstconfiguration uses a fiber matrix having a lattice of channels extendingthrough the matrix. The matrix is supported in a culture vesselpartially filled with culture medium. The medium is pumped into andthrough the matrix. The system further includes a filter placed in-linewith the pump for extracting desired cell products and/or purifying themedium of cell bi-products. Suitable heating and gas-supply means formaintaining desired gas and temperature control of the medium may alsobe employed, as well as means for replenishing the medium. A second cellculture configuration utilizes a multi-plate matrix. The plates in thematrix are submerged in a suitable cell culture medium in a vessel, andthe medium is circulated, through the plates by a pump. Theconfiguration may also include a filter and culture control means, asindicated above.

In a third configuration, the matrix is present as fragments which aresuspended in a culture medium. The matrix fragments are producedpreferably by fragmentizing matrix plates of having a thickness betweenabout 0.2 to 2 mm. The matrix fragments, being slightly denser than theculture medium, can be maintained in a suspended state, by gentlestirring or gas bubbling, and can be separated readily from the mediumby settling, centrifugation or filtration.

It will be understood that the matrix in the configurations is firststerilized, conventionally, and may be further treated to preabsorbagents which promote cell adhesion to the substrate. Typically theseagents include a divalent cation, such as Mg⁺², and a glycoprotein suchas fibronectin, polyethylene, and/or fibrinogen. The pretreatmentpreferably involves incubating the sterilized matrix in a serum or othermedium containing the growth factors of interest.

Alternatively, the fibers, meaning either silica or polymer fibers, maybe derivatized by covalent attachment of desired growth factors, such asbone osteogenic factor, cytokines, or the like. Methods for derivatizingthe free hydroxyl groups on silica fibers, or free hydroxyl, amine,carboxyl, suldydryl, or aldehyde groups that may be present on polymerfibers are well known.

B. Implantable Cell Matrix

In another general application, the matrix of the invention is used asan implantable substrate for supporting cell growth in vivo. As oneexample of this application, a hip replacement device having a stemdesigned to be inserted and locked into the femur of subject, and a ballwhich will serve as the ball of the repaired hip joint. The stem has atitanium inner core which is formed integrally with the ball. The coveris ensheathed in a fused-fiber matrix constructed according to theinvention, and which forms a covering over the core. The matrix coveringis preferably formed by machining a fused-fiber block of the typedescribed above. The covering may be attached to the stem core by asuitable adhesive, or by heat fusion near the melt temperature of thetitanium, in the case of a silica and/or alumina fiber matrix.

In operation, the matrix on the stem provides a substrate for the growthand infusion of osteoblast cells, acting to weld the stem to the bonethrough a biological bone structure. The matrix fibers may include bonegrowth factors for promoting bone cell growth into the matrix.

An implantable cell substrate device can be constructed according to theinvention. The device is designed for use as an implantable substratefor supporting growth of a selected tissue cells, such as pancreaticcells or fibroblasts, capable of producing desired cell metabolites suchas insulin or interferon.

This device has a tubular construction, and provides a spiraled innercore for supporting cell growth, while allowing body fluids to bathe thecells, bringing nutrients and removing cell products. The device isformed preferably by machining a block of fused-fiber matrix of the typedisclosed herein. The outer surface of the device is coated with abiocompatible material, such as silicon rubber to insulate the fibermatrix from direct contact with the surrounding tissue.

In operation, the device is seeded with the desired cells in culture,preferably until the spiraled core has a maximum cell density. Thedevice is then implanted into a desired tissue region, e.g., anintramuscular site.

The two examples described above illustrate two of a variety of implantdevices, for bone repair, bone replacement, and tissue-cell augmentationor replacement that may be prepared using the cell-substrate matrixmaterial of the invention.

Utility: Chromatography

The silica-fiber matrix of the invention is also useful for chemical andcell chromatographic separations.

In one embodiment, the matrix can serve as a substrate for thin-layerchromatographic separations, using well-known solvent-systems anddevelopment conditions. The matrix in this application is preferably athin matrix plate, formed, for example, by slicing a matrix block to adesired thickness, e.g., between 1–3 mm. Alternatively, thin plates maybe prepared by slurry settling, as described above, in thin-plate molds.

In a related aspect, the matrix serves the role of a silica gel columnfor chemical separations by silica gel chromatography. As above, thematrix may be machined from a block matrix mold, or formed by settlingin a suitable cylindrical mold. For both applications, the density ofthe matrix is preferably above the 3.5–5.5 pounds/ft³ matrix densitythat is employed for cell culture.

According to another aspect of the invention, the fused-fiber matrixmaterial having a density between about 3.5 and 5.5 pounds/ft³ is usefulfor cell-separation chromatography, and typically for use in separatingcells and other particles above about 1 micron in size from serumcomponents in a blood sample.

A diagnostic test strip can be prepared for use in detecting a serumcomponents, such as glucose, cholesterol, or a cholesterol-containinglipoprotein, such as low density lipoprotein or high-density lipoproteinparticles. The strip, which is formed of the fused-silica fiber matrixmaterial of the invention, includes an application site at one strip enda detection site at the opposite end. The detection site may includereagents for producing a detectable color signal in the presence of aselected serum analyte. Alternatively, serum from this site may betransferred by physical contact to a separate reagent pad.

In operation, a blood sample, e.g., a 25–200μ sample, is added to theapplication site, and the sample is drawn by capillarity toward thestrip's opposite end. Migration of the sample through the interstices ofthe matrix acts to retard the migration rate of larger particles,including blood cells, causing separation of the blood cells separatedinto a slower migrating blood cell fraction and a faster-migrating serumfraction, which is received at the detection site free of blood cells.Analyte detection may occur at this site, or a separate detection padmay be brought in contact with the strip site, to draw serum into thepad.

METHODS OF USE

Drugs or other biologically active materials can be incorporated intothe materials, making the materials a drug delivery device. The devicecan be implanted into an animal. The density of the material and theloading of the drug can be altered in order to modulate the time releaseproperty of the device. The drug can be a small molecule organic, aprotein, a peptide, a nucleic acid, a growth factor, or any otherbiologically active substance.

The materials can be used as a filler material. Filler materials can beused to reinforce organic, inorganic, or metallic materials. The fillermaterials can be used to reinforce polymers. The materials can be usedas a composite filler for collagen.

All of the compositions and/or methods disclosed and claimed herein canbe made and executed without undue experimentation in light of thepresent disclosure. While the compositions and methods of this inventionhave been described in terms of preferred embodiments, it will beapparent to those of skill in the art that variations may be applied tothe compositions and/or methods and in the steps or in the sequence ofsteps of the methods described herein without departing from theconcept, spirit and scope of the invention. More specifically, it willbe apparent that certain agents which are both chemically andphysiologically related may be substituted for the agents describedherein while the same or similar results would be achieved. All suchsimilar substitutes and modifications apparent to those skilled in theart are deemed to be within the spirit, scope and concept of theinvention.

What is claimed is:
 1. A high density porous composition comprising: upto about 100% by weight silica wherein the silica comprises from about50% to about 100% by weight cristobalite; up to about 60% by weightalumina; and an additional metal oxide; wherein the composition has adensity of at least about 12 pounds per cubic foot, a mean pore diameterof about 50 microns to about 600 microns, at least about 50% of theexposed surface area is silicon dioxide, said surface modified by achemical reaction to increase its hydrophilicity or hydrophobicity. 2.The composition of claim 1, further comprising tantalum oxide orzirconium oxide.
 3. The composition of claim 1, further comprisingcarbon fiber.
 4. The composition of claim 1, further comprising a drug.5. The composition of claim 1, further comprising silica gel.
 6. Thecomposition of claim 1, wherein the density is at least about 24 poundsper cubic foot (128 kg/m3).
 7. The composition of claim 1, wherein thedensity is at least about 48 pounds per cubic foot (192 kg/m3).
 8. Thecomposition of claim 1, wherein the density is at least about 36 poundsper cubic foot (577 kg/m3).
 9. The composition of claim 1, wherein thedensity is at least about 64 pounds per cubic foot (1025 kg/m3).
 10. Thecomposition of claim 1, wherein the exposed surface is at least about75% silicon dioxide.
 11. The composition of claim 1, wherein the exposedsurface is at least about 95% silicon dioxide.
 12. The composition ofclaim 5, wherein the silica gel reinforces the composition.
 13. Thecomposition of claim 1, wherein the chemical reaction to increase thehydrophilicity or hydrophobicity of the surface area comprises reactionwith a hydroxide.